Cetuximab, Paclitaxel, Carboplatin, and Radiation Therapy in Treating Patients With Unresectable Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

• Determine the feasibility of cetuximab when administered concurrently with paclitaxel, carboplatin, and radiotherapy, in terms of safety and compliance, in patients with unresectable stage IIIA or IIIB non-small cell lung cancer.

Secondary

• Determine the response rate (complete and partial) in patients treated with this regimen.
• Determine the overall survival (1- and 2-year survival rate and median survival) of patients treated with this regimen.
• Determine the time to disease progression (at 1 and 2 years) in patients treated with this regimen.
• Correlate epidermal growth factor receptor expression with the toxicity of this regimen and response, overall survival, and progression in these patients.

OUTLINE: This is a multicenter study.

• Cetuximab loading dose (week 1): Patients receive a loading dose of cetuximab IV over 2 hours on day 1.
• Concurrent cetuximab and chemoradiotherapy (weeks 2-8): Patients receive cetuximab IV over 1 hour, paclitaxel IV over 1 hour, and carboplatin IV over 30 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients undergo radiotherapy once daily on days 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50-53.
• Consolidation therapy (weeks 9-17): Patients receive cetuximab IV over 1 hour on days 57, 64, 71, 78, 85, 92, 99, 106, and 113. Patients also receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on days 78 and 99.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days, every 3 months for 2 years, every 4 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 84 patients will be accrued for this study within 1 year.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) of 1 of the following subtypes:

• Squamous cell carcinoma
• Adenocarcinoma (including bronchoalveolar cell)
• Large cell anaplastic carcinoma (including giant and clear cell carcinomas)
• Poorly differentiated/not otherwise specified NSCLC
• Stage IIIA (T1-2, N2, M0 or T3, N1-2, M0) or IIIB (T4, any N, M0 or any T, N2-3, M0)

• If the largest mediastinal node is < 2.0 cm in diameter and this is the basis for stage III disease, then at least 1 of the nodes must be cytologically or histologically positive
• Unresectable disease

• No totally resected tumors
• Tumors adjacent to a vertebral body allowed provided all gross disease can be encompassed in the radiation boost field and the boost volume is limited to < 50% of the ipsilateral lung volume
• Measurable disease
• Transudate, cytologically negative, non-bloody pleural effusions allowed provided the tumor can be encompassed within a reasonable field of radiotherapy

• Pleural effusions seen on a chest CT scan are allowed provided they are not visible on a chest x-ray and are too small to tap
• No asymptomatic or symptomatic brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL (transfusion independent)

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• SGOT (serum glutamic oxaloacetic transaminase) or SGPT (serum glutamate pyruvate transaminase) ≤ 3 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• No significant history of cardiac disease
• No uncontrolled hypertension
• No unstable angina
• No uncompensated congestive heart failure
• No myocardial infarction within the past year
• No cardiac ventricular arrhythmias requiring medication
• LVEF (left ventricular ejection fraction) normal by MUGA (multi-gated acquisition) scan or echocardiogram

Pulmonary

• No history of interstitial pneumonitis
• No history of severe chronic obstructive pulmonary disease requiring 3 or more hospitalizations within the past year
• FEV_1 ≥ 1,200 cc
• No active pulmonary infection unresponsive to conventional antibiotics

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after study therapy
• Glucose ≤ 2 times ULN
• No more than 5% weight loss within the past 3 months
• No known allergy to murine proteins or Cremophor EL
• No neuropathy grade 2 or greater
• No other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other in situ cancers

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior drugs that target the epidermal growth factor receptor pathway
• No prior chimerized monoclonal antibody therapy
• No other concurrent immunotherapy
• No concurrent colony-stimulating factors (i.e., filgrastim [G-CSF] and sargramostim [GM-CSF])

• Concurrent epoetin alfa allowed

Chemotherapy

• No prior systemic chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy except hormones for non-disease-related conditions (e.g., insulin for diabetes) or steroids for acute symptom management, adrenal failure, septic shock, or as antiemetics

Radiotherapy

• No prior thoracic or neck radiotherapy
• No concurrent intensity-modulated radiotherapy

Surgery

• Recovered from prior exploratory thoracotomy
• No prior surgical resection of the present cancer

Other

• More than 30 days since prior participation in another clinical trial
• No concurrent participation in another clinical trial
• No other concurrent anticancer therapy
• No amifostine during or for 3 months after study radiotherapy